INTRODUCTION: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. RESULTS: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. CONCLUSIONS: Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.
INTRODUCTION: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. RESULTS: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. CONCLUSIONS:Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.
Authors: Rafael Rosell; Enric Carcereny; Radj Gervais; Alain Vergnenegre; Bartomeu Massuti; Enriqueta Felip; Ramon Palmero; Ramon Garcia-Gomez; Cinta Pallares; Jose Miguel Sanchez; Rut Porta; Manuel Cobo; Pilar Garrido; Flavia Longo; Teresa Moran; Amelia Insa; Filippo De Marinis; Romain Corre; Isabel Bover; Alfonso Illiano; Eric Dansin; Javier de Castro; Michele Milella; Noemi Reguart; Giuseppe Altavilla; Ulpiano Jimenez; Mariano Provencio; Miguel Angel Moreno; Josefa Terrasa; Jose Muñoz-Langa; Javier Valdivia; Dolores Isla; Manuel Domine; Olivier Molinier; Julien Mazieres; Nathalie Baize; Rosario Garcia-Campelo; Gilles Robinet; Delvys Rodriguez-Abreu; Guillermo Lopez-Vivanco; Vittorio Gebbia; Lioba Ferrera-Delgado; Pierre Bombaron; Reyes Bernabe; Alessandra Bearz; Angel Artal; Enrico Cortesi; Christian Rolfo; Maria Sanchez-Ronco; Ana Drozdowskyj; Cristina Queralt; Itziar de Aguirre; Jose Luis Ramirez; Jose Javier Sanchez; Miguel Angel Molina; Miquel Taron; Luis Paz-Ares Journal: Lancet Oncol Date: 2012-01-26 Impact factor: 41.316
Authors: David R Jones; Christopher A Moskaluk; Heidi H Gillenwater; Gina R Petroni; Sandra G Burks; Jennifer Philips; Patrice K Rehm; Juan Olazagasti; Benjamin D Kozower; Yongde Bao Journal: J Thorac Oncol Date: 2012-11 Impact factor: 15.609
Authors: Michael Boyer; Keith Horwood; Nick Pavlakis; Paul De Souza; Michael Millward; Brian Stein; Michael Johnston; Fiona Abell; Danny Rischin Journal: Asia Pac J Clin Oncol Date: 2012-05-15 Impact factor: 2.601
Authors: Giorgio V Scagliotti; Paul Germonpré; Leon Bosquée; Johan Vansteenkiste; R Gervais; David Planchard; Martin Reck; Filippo De Marinis; Jin Soo Lee; Keunchil Park; Bonne Biesma; Steven Gans; R Ramlau; Aleusandra Szczesna; A Makhson; G Manikhas; Bruno Morgan; Y Zhu; Kai C Chan; Joachim von Pawel Journal: Lung Cancer Date: 2009-08-18 Impact factor: 5.705
Authors: Anne M Traynor; Sarita Dubey; Jens C Eickhoff; Jill M Kolesar; Kathleen Schell; Michael S Huie; David L Groteluschen; Sarah M Marcotte; Courtney M Hallahan; Hilary R Weeks; George Wilding; Igor Espinoza-Delgado; Joan H Schiller Journal: J Thorac Oncol Date: 2009-04 Impact factor: 15.609
Authors: D Ross Camidge; Yung-Jue Bang; Eunice L Kwak; A John Iafrate; Marileila Varella-Garcia; Stephen B Fox; Gregory J Riely; Benjamin Solomon; Sai-Hong I Ou; Dong-Wan Kim; Ravi Salgia; Panagiotis Fidias; Jeffrey A Engelman; Leena Gandhi; Pasi A Jänne; Daniel B Costa; Geoffrey I Shapiro; Patricia Lorusso; Katherine Ruffner; Patricia Stephenson; Yiyun Tang; Keith Wilner; Jeffrey W Clark; Alice T Shaw Journal: Lancet Oncol Date: 2012-09-04 Impact factor: 41.316
Authors: Yujie Zhao; Nathan R Foster; Jeffrey P Meyers; Sachdev P Thomas; Donald W Northfelt; Kendrith M Rowland; Bassam I Mattar; David B Johnson; Julian R Molina; Sumithra J Mandrekar; Steven E Schild; James D Bearden; Marie-Christine Aubry; Alex A Adjei Journal: J Thorac Oncol Date: 2015-01 Impact factor: 15.609
Authors: Ji-Youn Han; Soo Hyun Lee; Geon Kook Lee; Tak Yun; Young Joo Lee; Kum Hui Hwang; Jin Young Kim; Heung Tae Kim Journal: Cancer Chemother Pharmacol Date: 2015-01-01 Impact factor: 3.333